PK/PD of Vitamin D3 in Adults With CF

University of Southern California

Status

Terminated

Conditions

Vitamin D Deficiency

Cystic Fibrosis

Treatments

Dietary Supplement: Vitamin D3

Study type

Interventional

Funder types

Other

Identifiers

NCT03734744

HS-18-00737

Details and patient eligibility

About

Despite the extensive literature on adverse clinical outcomes associated with vitamin D deficiency, there are currently no proven treatment strategy that effectively achieves and maintains optimal serum vitamin D status in cystic fibrosis (CF) patients. For the treatment of vitamin D deficiency, CF Foundation currently recommends 2,000 IU daily. However, because achieving adequate serum 25(OH)D levels is a challenge in CF, higher doses of vitamin D may be necessary to reach and maintain vitamin D sufficiency. Poor oral bioavailability of ergocalciferol has been demonstrated in CF patients, which may potentially also be an issue with cholecalciferol. In order to optimize the treatment of vitamin D deficiency in CF, the kinetic disposition must be well understood. However, there are very few data currently available describing the kinetics of both vitamin D and 25-hydroxyvitamin D, and to the investigator's knowledge, no studies have yet characterized the pharmacokinetic disposition of vitamin D and its metabolites in cystic fibrosis. Addressing this issue is crucial in effectively and safely correcting vitamin D deficiency in CF.

Full description

Clinically stable CF patients with a history of pancreatic insufficiency (n=6) and matching non-CF subjects (n=6) will be recruited in this study. All subjects will be pre-screened for 25(OH)D status to include those with 25(OH)D levels below 30 ng/mL. The subjects will receive a single oral dose (300,000 - 600,000 IU) of vitamin D3, and the dose will be based on study participant's baseline 25-hydroxyvitamin D3 level. For CF patients, the dose will be administered with food and pancreatic enzyme supplement. This dose was chosen as previous studies in pediatric CF patients demonstrated that a large single dose of up to 600,000 IU vitamin D3 raised and maintained sufficient 25(OH)D concentrations without any signs of adverse events.

Enrollment

6 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

For CF, diagnosis of CF based on positive sweat chloride or known CF mutation
For CF, Patients with pancreatic insufficiency
Age ≥ 18 years
Serum 25(OH)D concentrations below 30 ng/mL (75 nmol/L)

Exclusion criteria

Pregnancy
History of lung transplant,
Severe anemia (hemoglobin concentration < 7 g/dL),
Liver disease (AST/ALT > 3x ULN), kidney disease (GFR ≤ 40 mL/min), or granulomatous conditions
Patients taking steroids, cholesterol-lowering drug (cholestyramine), weight-loss drugs (orlistat) , statins, anti-tuberculosis drugs (rifampin and isoniazid), phenobarbital, phenytoin, carbamazepine, immunosuppressants (cyclosporine, tacrolimus)